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1.
Gynecol Oncol ; 183: 47-52, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503141

RESUMO

INTRODUCTION: Gynecologic and breast cancers share several risk factors. Breast cancer risk assessment tools can identify those at elevated risk and allow for enhanced breast surveillance and chemoprevention, however such tools are underutilized. We aim to evaluate the use of routine breast cancer risk assessment in a gynecologic oncology clinic. METHODS: A patient-facing web-based tool was used to collect personal and family history and run four validated breast cancer risk assessment models (Tyrer-Cuzick (TC), Gail, BRCAPRO, and Claus) in a gynecologic oncology clinic. We evaluated completion of the tools and identification of patients at elevated risk for breast cancer using the four validated models. RESULTS: A total of 99 patients were included in this analysis. The BRCAPRO model had the highest completion rate (84.8%), followed by the TC model (74.7%), Gail model (74.7%), and the Claus model (52.1%). The TC model identified 21.6% of patients completing the model as having ≥20% lifetime risk of breast cancer, compared to 6.8% by the Gail model, and 0% for both the BRCAPRO and Claus models. The Gail model identified 52.5% of patients as having ≥1.67% 5-year risk of breast cancer. Among patients identified as high-risk for breast cancer and eligible for screening, 9/9 (100%) were referred to a high-risk breast clinic. CONCLUSION: Among patients that completed the TC breast cancer risk assessment in a gynecologic oncology clinic, approximately 1 in 5 were identified to be at significantly elevated lifetime risk for breast cancer. The gynecologic oncologist's office might offer a convenient and feasible setting to incorporate this risk assessment into routine patient care, as gynecologic oncologists often have long-term patient relationships and participate in survivorship care.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Medição de Risco/métodos , Pessoa de Meia-Idade , Adulto , Idoso , Neoplasias dos Genitais Femininos , Medicina de Precisão/métodos , Sobrevivência
2.
J Cancer Educ ; 38(4): 1163-1169, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36454364

RESUMO

The lesbian, gay, bisexual, transgender, queer/questioning and two-spirited, plus (LGBTQ2 +) community experiences cancer-related health disparities and inequities. Our objective was to assess LGBTQ2 + knowledge, attitudes, practices and education interest of healthcare professionals (HCPs), identify opportunities to improve care and inform the development of an HCP education curriculum. This was a mixed methods quality improvement study conducted within a tertiary academic cancer centre. An email was sent to all gynaecologic oncology disease site staff (n = 92) with a secure link to an online survey. We measured respondents' sociodemographic characteristics and LGBTQ2 + knowledge, attitudes, practice behaviours and education interest. Open comments explored HCP experiences and reservations caring for LGBTQ2 + patients and suggestions to improve care. Seventy-five out of ninety-two (82%) HCPs completed the survey, with 7% identifying as LGBTQ2 + . HCPs reported feeling less comfortable (88% vs. 80%, p = 0.031) and knowledgeable (44% vs. 27%, p < 0.001) caring for transgender patients compared to LGBQ2 + patients. Most (76%) were unaware whether LGBTQ2 + -specific patient educational materials existed within their institution. Almost all (92% strongly agreed/agreed) were interested in receiving LGBTQ2 + -specific education. Two themes emerged from analysis of open comments: (i) HCPs are concerned of offending LGBTQ2 + individuals because of their lack of knowledge and (ii) HCPs desire LGBTQ2 + -specific health training, specifically in asking pronouns and caring for transgender patients. HCPs report competency gaps in caring for LGBTQ2 + patients with cancer but desire education. In response, we recommend institutions develop an educational curriculum for HCPs improve communication and inclusivity in cancer care.


Assuntos
Neoplasias , Minorias Sexuais e de Gênero , Feminino , Humanos , Conhecimentos, Atitudes e Prática em Saúde , Comportamento Sexual , Pessoal de Saúde/educação , Atitude do Pessoal de Saúde , Neoplasias/terapia
3.
Ann Surg Oncol ; 29(13): 8469-8477, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35989390

RESUMO

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial II (MSLT-II) led to a change in the management of tumor-positive sentinel lymph nodes (SLNs) from completion node dissection (CLND) to nodal observation. This study aimed to evaluate prognostic factors for predicting sentinel node basin recurrence (SNBR) using data from MSLT-II trial participants. METHODS: In MSLT-II, 1076 patients were treated with observation. Patients were included in the current study if they had undergone a post-sentinel node basin ultrasound (PSNB-US) within 4 months after surgery. The study excluded patients with positive SLN by reverse transcription-polymerase chain reaction (RT-PCR) or incomplete SLN pathologic data. Primary tumor, patient, PSNB-US, and SLN characteristics were evaluated. Multivariable regression analyses were performed to determine independent prognostic factors associated with SNBR. RESULTS: The study enrolled 737 patients: 193 (26.2%) patients with SNBR and 73 (9.9%) patients with first abnormal US. The patients with an abnormal first US were more likely to experience SNBR (23.8 vs. 5.0%). In the multivariable analyses, increased risk of SNBR was associated with male gender (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.00-1.9; p = 0.049), increasing Breslow thickness (aHR, 1.10; 95% CI, 1.01-1.2; p = 0.038), presence of ulceration (aHR, 1.93; 95% CI, 1.42-2.6; p < 0.001), sentinel node tumor burden greater than 1 mm (aHR, 1.91; 95% CI, 1.10-3.3; p = 0.022), lymphovascular invasion (aHR, 1.53; 95% CI, 1.00-2.3; p = 0.048), and presence of abnormal PSNB-US (aHR, 4.29; 95% CI, 3.02-6.1; p < 0.001). CONCLUSIONS: The first postoperative US together with clinical and pathologic factors may play an important role in predicting SNBR.


Assuntos
Linfadenopatia , Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Masculino , Humanos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Prognóstico , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Melanoma/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Excisão de Linfonodo , Linfadenopatia/cirurgia , Síndrome
4.
Exp Physiol ; 107(8): 906-918, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35561231

RESUMO

NEW FINDINGS: What is the central question of this study? Do obesity and acute resistance exercise alter the regulation of muscle intercellular communication pathways consistent with inadequate compensatory angiogenesis in response to muscle loading present in individuals with obesity? What is the main finding and its importance? Obesity is associated with differences in both pro- and anti-angiogenic signalling consistent with lower muscle capillarization. Acute resistance exercise increases the release of skeletal muscle small extracellular vesicles independent of body mass. These results identify new cellular factors associated with impaired angiogenesis in obesity and the positive effects of acute resistance exercise in lean and obese skeletal muscle. ABSTRACT: Obesity (OB) impairs cell-to-cell communication signalling. Small extracellular vesicles (EVs), which include exosomes, are released by skeletal muscle and participate in cell-to-cell communication, including the regulation of angiogenesis. Resistance exercise (REx) increases muscle fibre size and capillarization. Although obesity increases muscle fibre size, there is an inadequate increase in capillarization such that capillary density is reduced. It was hypothesized that REx-induced angiogenic signalling and EV biogenesis would be lower with obesity. Sedentary lean (LN) and OB subjects (n = 8 per group) performed three sets of single-leg knee-extension REx at 80% of maximum. Muscle biopsies were obtained at rest, 15 min and 3 h postexercise and analysed for angiogenic and EV biogenesis mRNA and protein. In OB subjects, muscle fibre size was ∼20% greater and capillary density with type II fibres ∼25% lower compared with LN subjects (P < 0.001). In response to REx, the increase in VEGF mRNA (pro-angiogenic) was similar (3-fold) between groups, while thrombospondin-1 (TSP-1) mRNA (anti-angiogenic) increased ∼2.5-fold in OB subjects only (P = 0.010). miR-130a (pro-angiogenic) was ∼1.4-fold (P = 0.011) and miR-503 (anti-angiogenic) ∼1.8-fold (P = 0.017) greater in OB compared with LN subjects at all time points. In both groups, acute REx decreased the EV surface protein Alix by ∼50%, consistent with the release of exosomes (P = 0.016). Acute REx appears to induce the release of skeletal muscle small EVs independent of body mass. However, with obesity there is predominantly impaired angiogenic signalling, consistent with inadequate angiogenesis in response to basal muscle hypertrophy.


Assuntos
Músculo Esquelético , Neovascularização Fisiológica , Obesidade , Treinamento Resistido , Humanos , MicroRNAs/metabolismo , Músculo Esquelético/fisiologia , Obesidade/metabolismo , RNA Mensageiro/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
J Neurooncol ; 157(1): 157-163, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35092549

RESUMO

BACKGROUND: Metastasis is the most common brain tumor in adults. It is the standard of care at most North American centers to obtain an early postoperative imaging after their resection. However, the necessity of this practice in the absence of a new postoperative deficit remains unclear. METHODS: We retrospectively reviewed our surgical cohort of patients who underwent resection of brain metastases from July 2018 to June 2019. We collected demographic data and reviewed results of routine postoperative CT scans and neurological morbidities to examine the diagnostic and therapeutic yield of an early postoperative scan. In addition, we performed a systematic review of the topic. RESULTS: Our review included 130 patients, all of whom underwent gross total resection of one or more brain metastases. On postoperative CT, none had unexpected findings such as cavity hematoma or new ischemia; no changes in management resulted from postoperative imaging. One patient required a higher dose of dexamethasone on postoperative day 4 for delayed hemiparesis and aphasia due to cerebral edema. Three additional patients underwent a wound washout for delayed infection during a subsequent admission. Our systematic review identified three additional studies; in a combined cohort of 450 patients (including our own), no patients had clinically actionable findings on routine postoperative CT. CONCLUSIONS: Following resection of brain metastases, a routine postoperative CT scan has low diagnostic yield and did not change patient management in any cases examined in this work.


Assuntos
Neoplasias Encefálicas , Tomografia Computadorizada por Raios X , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Craniotomia , Humanos , Período Pós-Operatório , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
6.
Eur J Appl Physiol ; 120(12): 2835-2846, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32989478

RESUMO

PURPOSE: Obesity is associated with numerous changes in skeletal muscle including greater muscle mass and muscle fiber cross sectional area (FCSA), yet fasted muscle protein synthesis is lower. Activation of the IGF-1/Akt/mTOR pathway is critical for muscle mass maintenance, muscle hypertrophy, and muscle protein regulation. Resistance exercise (RE) increases muscle mass, FCSA, and IGF-1. Persons with obesity have greater skeletal muscle mass and larger skeletal muscle fiber cross sectional area. The IGF-1/Akt/mTOR pathway is critical for the regulation of skeletal muscle mass. Our study found men and women with obesity have lower skeletal muscle IGF-1 mRNA and protein and higher expression of miR-206 an epigenetic regulator of IGF-1, at rest and following an acute bout of resistance exercise. Despite this, Akt mediated signaling was maintained and maintenance of phosphorylation does not appear to be accounted for by compensatory pathways. Our findings suggest a possible negative feedback mechanism via increased miR-206 and in turn decreased IGF-1 to limit further skeletal muscle hypertrophy in persons with obesity. The current work investigated if: (1) obesity dysregulates basal skeletal muscle IGF-1 pathways; and (2) obesity augments the muscle IGF-1 pathway responses to acute RE. METHODS: Eight sedentary (no self-reported physical activity), lean (LN) and eight sedentary subjects with obesity (OB) had vastus lateralis biopsies taken at rest, and 15 min and 3 h post-acute RE for the measurement of the IGF-1 pathway and muscle FCSA. RESULTS: Type II FCSA was larger in OB vs. LN. Skeletal muscle IGF-1 mRNA and IGF-1 protein were lower in OB vs. LN at rest and post-exercise. Acute RE increased IGF-1 protein similarly in both groups. The expression of miR-206, a post-transcriptional inhibitor of IGF-1 expression, was higher in OB vs. LN and linked with lower IGF-1 mRNA (r = - 0.54). CONCLUSION: In spite of greater muscle FCSA, muscle IGF-1 expression was lower in obesity suggesting negative feedback may be limiting muscle mass expansion in obesity.


Assuntos
Exercício Físico/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Feminino , Humanos , Masculino , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/metabolismo , Fosforilação/fisiologia , RNA Mensageiro/metabolismo , Treinamento Resistido/métodos , Transdução de Sinais/fisiologia
8.
Ann Intern Med ; 166(6): 419-429, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28114673

RESUMO

BACKGROUND: Recent guidelines recommend a systolic blood pressure (SBP) goal of less than 150 mm Hg for adults aged 60 years or older, but the balance of benefits and harms is unclear in light of newer evidence. PURPOSE: To systematically review the effects of more versus less intensive BP control in older adults. DATA SOURCES: Multiple databases through January 2015 and MEDLINE to September 2016. STUDY SELECTION: 21 randomized, controlled trials comparing BP targets or treatment intensity, and 3 observational studies that assessed harms. DATA EXTRACTION: Two investigators extracted data, assessed study quality, and graded the evidence using published criteria. DATA SYNTHESIS: Nine trials provided high-strength evidence that BP control to less than 150/90 mm Hg reduces mortality (relative risk [RR], 0.90 [95% CI, 0.83 to 0.98]), cardiac events (RR, 0.77 [CI, 0.68 to 0.89]), and stroke (RR, 0.74 [CI, 0.65 to 0.84]). Six trials yielded low- to moderate-strength evidence that lower targets (≤140/85 mm Hg) are associated with marginally significant decreases in cardiac events (RR, 0.82 [CI, 0.64 to 1.00]) and stroke (RR, 0.79 [CI, 0.59 to 0.99]) and nonsignificantly fewer deaths (RR, 0.86 [CI, 0.69 to 1.06]). Low- to moderate-strength evidence showed that lower BP targets do not increase falls or cognitive impairment. LIMITATION: Data relevant to frail elderly adults and the effect of multimorbidity are limited. CONCLUSION: Treatment to at least current guideline standards for BP (<150/90 mm Hg) substantially improves health outcomes in older adults. There is less consistent evidence, largely from 1 trial targeting SBP less than 120 mm Hg, that lower BP targets are beneficial for high-risk patients. Lower BP targets did not increase falls or cognitive decline but are associated with hypotension, syncope, and greater medication burden. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO 2015: CRD42015017677).


Assuntos
Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Acidentes por Quedas , Fatores Etários , Doenças Cardiovasculares/prevenção & controle , Transtornos Cognitivos/induzido quimicamente , Fraturas Ósseas/etiologia , Humanos , Hipotensão/induzido quimicamente , Nefropatias/induzido quimicamente , Pessoa de Meia-Idade , Qualidade de Vida , Medição de Risco , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle , Síncope/induzido quimicamente
10.
Curr Oncol ; 31(4): 2172-2184, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38668064

RESUMO

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are widely used in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) in first line (1L), but little is known about their real-world use and clinical outcomes long-term, in Canada. This study used Pentavere's previously validated artificial intelligence (AI) to extract real-world data on the treatment patterns and outcomes of patients receiving CDK4/6i+endocrine therapy (ET) for HR+/HER2- ABC/MBC at Sinai Health in Toronto, Canada. Between 1 January 2016 and 1 July 2021, 48 patients were diagnosed with HR+/HER2- ABC/MBC and received CDK4/6i + ET. A total of 38 out of 48 patients received CDK4/6i + ET in 1L, of which 34 of the 38 (89.5%) received palbociclib + ET. In 2L, 12 of the 21 (57.1%) patients received CDK4/6i + ET, of which 58.3% received abemaciclib. In 3L, most patients received chemotherapy (10/12, 83.3%). For the patients receiving CDK4/6i in 1L, the median (95% CI) time to the next treatment was 42.3 (41.2, NA) months. The median (95% CI) time to chemotherapy was 46.5 (41.4, NA) months. The two-year overall survival (95% CI) was 97.4% (92.4, 100.0), and the median (range) follow-up was 28.7 (3.4-67.6) months. Despite the limitations inherent in real-world studies and a limited number of patients, these AI-extracted data complement previous studies, demonstrating the effectiveness of CDK4/6i + ET in the Canadian real-world 1L, with most patients receiving palbociclib as CDK4/6i in 1L.


Assuntos
Aminopiridinas , Benzimidazóis , Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Inibidores de Proteínas Quinases , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Canadá , Idoso , Adulto , Inteligência Artificial , Resultado do Tratamento , Metástase Neoplásica , Piridinas/uso terapêutico , Piperazinas/uso terapêutico , Idoso de 80 Anos ou mais
11.
Artigo em Inglês | MEDLINE | ID: mdl-38754135

RESUMO

Importance: Accurate, timely, and cost-effective methods for staging oropharyngeal cancers are crucial for patient prognosis and treatment decisions, but staging documentation is often inaccurate or incomplete. With the emergence of artificial intelligence in medicine, data abstraction may be associated with reduced costs but increased efficiency and accuracy of cancer staging. Objective: To evaluate an algorithm using an artificial intelligence engine capable of extracting essential information from medical records of patients with oropharyngeal cancer and assigning tumor, nodal, and metastatic stages according to American Joint Committee on Cancer eighth edition guidelines. Design, Setting, and Participants: This retrospective diagnostic study was conducted among a convenience sample of 806 patients with oropharyngeal squamous cell carcinoma. Medical records of patients with staged oropharyngeal squamous cell carcinomas who presented to a single tertiary care center between January 1, 2010, and August 1, 2020, were reviewed. A ground truth cancer stage dataset and comprehensive staging rule book consisting of 135 rules encompassing p16 status, tumor, and nodal and metastatic stage were developed. Subsequently, 4 distinct models were trained: model T (entity relationship extraction) for anatomical location and invasion state, model S (numerical extraction) for lesion size, model M (sequential classification) for metastasis detection, and a p16 model for p16 status. For validation, results were compared against ground truth established by expert reviewers, and accuracy was reported. Data were analyzed from March to November 2023. Main Outcomes and Measures: The accuracy of algorithm cancer stages was compared with ground truth. Results: Among 806 patients with oropharyngeal cancer (mean [SD] age, 63.6 [10.6] years; 651 males [80.8%]), 421 patients (52.2%) were positive for human papillomavirus. The artificial intelligence engine achieved accuracies of 55.9% (95% CI, 52.5%-59.3%) for tumor, 56.0% (95% CI, 52.5%-59.4%) for nodal, and 87.6% (95% CI, 85.1%-89.7%) for metastatic stages and 92.1% (95% CI, 88.5%-94.6%) for p16 status. Differentiation between localized (stages 1-2) and advanced (stages 3-4) cancers achieved 80.7% (95% CI, 77.8%-83.2%) accuracy. Conclusion and Relevance: This study found that tumor and nodal staging accuracies were fair to good and excellent for metastatic stage and p16 status, with clinical relevance in assigning optimal treatment and reducing toxic effect exposures. Further model refinement and external validation with electronic health records at different institutions are necessary to improve algorithm accuracy and clinical applicability.

12.
Clin Transl Radiat Oncol ; 45: 100723, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38282910

RESUMO

Background: Stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as standard-of-care adjuvant treatment following surgery for brain metastasis (BrM). Concomitant with the adoption of adjuvant SRS, a new pattern of failure termed "Pachymeningeal failure" (PMF) has emerged. Methods: We reviewed a prospective registry of 264 BrM patients; 145 and 119 were treated adjuvantly with WBRT and SRS, respectively. The Cox proportional hazards model was used to identify variables correlating to outcomes. Outcomes were calculated using the cumulative incidence (CI) method. Univariate (UVA) and multivariate analyses (MVA) were done to identify factors associated with PMF. Results: CI of PMF was 2 % and 18 % at 12 months, and 2 % and 23 % at 24 months for WRBT and SRS, respectively (p < 0.001). The CI of classic leptomeningeal disease (LMD) was 3 % and 4 % at 12 months, and 6 % and 6 % at 24 months for WBRT and SRS, respectively (P = 0.67). On UVA, adjuvant SRS [HR 9.75 (3.43-27.68) (P < 0.001)]; preoperative dural contact (PDC) [HR 6.78 (1.64-28.10) (P = 0.008)]; GPA score [HR 1.64 (1.11-2.42) (P = 0.012)]; and lung EGFR/ALK status [HR 3.11 (1.02-9.45) (P = 0.045)]; were associated with PMF risk. On MVA, adjuvant SRS [HR 8.15 (2.69-24.7) (P < 0.001)]; and PDC [HR 6.28 (1.51-26.1) (P = 0.012)] remained associated with PMF. Conclusions: Preoperative dural contact and adjuvant SRS instead of adjuvant WBRT were associated with an increased risk of PMF. Strategies to improve pachymeningeal radiation coverage to sterilize at risk pachymeninges should be investigated.

13.
Curr Oncol ; 31(4): 1947-1960, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38668049

RESUMO

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC.


Assuntos
Inteligência Artificial , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Canadá , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Receptores ErbB/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Idoso de 80 Anos ou mais , Adulto
14.
Cancer Res Commun ; 4(2): 475-486, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38329392

RESUMO

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11-2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08-2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29-0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment. SIGNIFICANCE: Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.


Assuntos
Antineoplásicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Peritoneais , Neoplasias Retais , Humanos , Feminino , Neoplasias Colorretais/genética , Neoplasias Peritoneais/genética , Estudos Retrospectivos , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Genômica , Sistema de Registros
15.
16.
PLoS One ; 18(5): e0285008, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37235590

RESUMO

Breastfeeding is often considered principally a biological issue but success is impacted by the socio-ecological environment of the lactating parent. Identifying current attitudes towards breastfeeding is essential in the effort toward normalizing breastfeeding in communities, including university campuses. The study explored campus community knowledge, awareness, and attitudes about breastfeeding, including available resources and applicable laws on two university campuses in the southern United States. This cross-sectional, self-reporting study utilized the Iowa Infant Feeding Attitude Scale and an adaptation of the Breastfeeding Behavior Questionnaire to survey a convenience sample. Results revealed decreased awareness of protective laws, availability of private lactation space, and insufficient public appreciation of breastfeeding's unique advantages to both lactating parent and infant as barriers to breastfeeding. These findings will help develop additional breastfeeding strategies to improve university campus community breastfeeding initiatives.


Assuntos
Aleitamento Materno , Lactação , Feminino , Lactente , Humanos , Estados Unidos , Universidades , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e Questionários , Mães
17.
Am J Surg ; 225(1): 212-219, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36058752

RESUMO

BACKGROUND: Due to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise. STUDY DESIGN: Utilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death. RESULTS: Of 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT. CONCLUSION: For older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Idoso , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/cirurgia , Pancreatectomia , Terapia Neoadjuvante , Carcinoma Ductal Pancreático/cirurgia , Estudos Retrospectivos , Neoplasias Pancreáticas
18.
Eur J Trauma Emerg Surg ; 49(2): 795-801, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36273349

RESUMO

PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a well-validated method for the control of noncompressible truncal hemorrhage. In lower resource or battlefield settings, the need for arterial line setup and monitoring is problematic and potentially prohibitive. We sought to evaluate the accuracy and precision of a miniaturized portable device (Centurion COMPASS®) versus standard arterial pressure monitoring using standard ER-REBOA and partial REBOA (pREBOA) as a high-fidelity and space-/time-conserving alternative. METHODS: A total of 40 swine underwent a four-phase validation/precision study (each phase using five ER-REBOAs and five pREBOAs). Phases I/II evaluated accuracy with full and pREBOA in uninjured animals. Phases III/IV duplicated the previous phases but in a severe hemorrhagic shock model. Carotid and femoral pressures were monitored with both intra-arterial pressure systems and the COMPASS® device. The vascular flow was measured by aortic flow probes. Correlation and Bland-Altman analysis were performed. RESULTS: There was a strong correlation in accuracy testing of proximal and distal COMPASS® devices compared to standard intra-arterial pressure monitoring (r = 0.94, 0.8; p < 0.005) as well as during precision testing (r = 0.98, 0.89 p < 0.005) in the uninjured phases. Similar accuracy and reliability were demonstrated in hemorrhagic shock, with a strong correlation for the proximal and distal COMPASS® devices (r = 0.98, 0.97; p < 0.005), as well as during precision testing (r = 0.99, 0.95; p < 0.005) in both full and pREBOA scenarios. Bland-Altman analysis showed extremely low bias between the COMPASS® and arterial line for both proximal (bias = 1.9) and distal (bias = 0.8) pressure measurements. CONCLUSION: The COMPASS® provides accurate and precise pressure measurements during standard and partial REBOA in both uninjured and shock conditions. This device may help extend and enhance capability in any low-resource/battlefield settings, or even eliminate the need for standard intra-arterial invasive pressure monitoring and external setup.


Assuntos
Oclusão com Balão , Procedimentos Endovasculares , Choque Hemorrágico , Suínos , Animais , Choque Hemorrágico/terapia , Pressão Arterial , Reprodutibilidade dos Testes , Modelos Animais de Doenças , Aorta , Oclusão com Balão/métodos , Ressuscitação/métodos , Procedimentos Endovasculares/métodos
19.
Int J Radiat Oncol Biol Phys ; 116(2): 280-289, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563908

RESUMO

PURPOSE: Working parents, and a rising number of adults delivering care for aging relatives, experience numerous challenges in their personal, family, professional, and financial lives owing to multiple responsibilities. This study describes the experiences of Canadian radiation oncologist (RO) parents and family caregivers, reporting challenges that may exist in providing family care with clinical and academic work commitments. METHODS AND MATERIALS: Canadian ROs, via RO heads of departments in cancer centers across Canada, and physician members of the Canadian Association of Radiation Oncology were invited to participate in an anonymous online survey between November 2021 and January 2022. The survey focused on demographics, experiences of pregnancy and leave, parenting and adult caregiving responsibilities, and self-care. RESULTS: A total of 103 staff ROs (38%) completed the survey and 78 (75.7%) identified as having a parental (76 [89.7%]) and/or other family caregiver (8 [10.3%]) role; 41% were female and 59% were male, with no difference between genders in the number of children (median, 2; interquartile range, 1-3; P = .17). More female respondents took parental leave for their first child compared with male respondents (mean, 29 vs 6 weeks; P < .001). Of male respondents who started caring for their first child during residency, 27% took parental leave, compared with 77% who started caring for their first child as a staff member (P = .003). The majority of respondents described "always/usually" having collegial support for each pregnancy and parental leave. Both genders described parental responsibilities as negatively affecting attendance at conferences (male, 65%; female, 77%; P = .31) and early or late work-related meetings (male, 76%; female, 79%; P = 1.0). More female respondents described parental responsibilities as negatively affecting their career (50% vs 29%; P = .085). Of female respondents, 52% (vs 26% of male respondents; P = .044) identified a physician mentor or positive role model around parenting issues. CONCLUSIONS: Parental and other family caregiving responsibilities are not gender unique in Canadian ROs, but competing work and family roles may affect genders differently.


Assuntos
Cuidadores , Radio-Oncologistas , Adulto , Criança , Gravidez , Humanos , Masculino , Feminino , Canadá , Espécies Reativas de Oxigênio , Pais , Inquéritos e Questionários
20.
Cancers (Basel) ; 15(10)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37345175

RESUMO

PURPOSE: To retrospectively review the clinical outcomes of patients with metastatic breast cancer (MBCa) following liver directed ablative intent radiotherapy (RT). METHODS: Demographics, disease and treatment characteristics of patients with MBCa who received liver metastasis (LM) directed ablative RT between 2004-2020 were analysed. The primary outcome was local control (LC), secondary outcomes included overall survival (OS) and progression-free survival (PFS) analyzed by univariate (UVA) and multi-variable analysis (MVA). RESULTS: Thirty MBCa patients with 50 LM treated with 5-10 fraction RT were identified. Median follow-up was 14.6 (range 0.9-156.2) months. Class of metastatic disease was described as induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (three patients, 10%). Median size of treated LM was 3.1 cm (range 1-8.8 cm) and median biologically effective dose delivered was 122 (Q1-Q3; 98-174) Gy3. One-year LC rate was 100%. One year and two-year survival was 89% and 63%, respectively, with size of treated LM predictive of OS (HR 1.35, p = 0.023) on UVA. Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p = 0.01) on UVA, trending to significance on MVA (HR 3.23, p = 0.051). CONCLUSIONS: Hypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC.

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